Prenatal exposure to mixtures of xenoestrogens and genome-wide DNA methylation in human placenta

Epigenomics. 2016 Jan;8(1):43-54. doi: 10.2217/epi.15.91. Epub 2015 Dec 18.

Abstract

Background: In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation.

Materials & methods: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas.

Results: No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B.

Conclusion: Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated.

Keywords: DNA methylation; TEXB; endocrine disruptors; epigenome xenoestrogens; placenta; prenatal; programming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Birth Weight
  • Carrier Proteins / genetics
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Estrogens / toxicity*
  • Female
  • Genome-Wide Association Study / methods*
  • Humans
  • KCNQ1 Potassium Channel / genetics
  • LDL-Receptor Related Protein-Associated Protein / genetics
  • Male
  • Placenta / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics*
  • RNA-Binding Proteins
  • Sex Factors
  • Thiolester Hydrolases / genetics

Substances

  • Carrier Proteins
  • Estrogens
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • LDL-Receptor Related Protein-Associated Protein
  • PPARGC1B protein, human
  • RNA-Binding Proteins
  • Thiolester Hydrolases
  • hydroxyacylglutathione hydrolase